Overman rearrangements

The Overman Rearrangement describes the [3,3]-aza-oxa-Cope sigmatropic rearrangement of A -allyltrichloroacetimidates to iV-allyltrichloroacetamides. This rearrangement has become the preferred method for converting allylic alcohols to transposed allylic amines and their derivatives. 

In some cases, the mercury(II)- and palladium(II)-catalysed allylic Overman rearrangement of trichloroacetimidates can be accomplished under mild conditions at room temperature or even much lower temperature. For example, the trichloroacetimidic ester of geraniol 12 is converted to linalyl trichloroacetamide 13 when treated with 0.2 equiv of mercuric trifluoroacetate at room temperature for 10 min. This catalytic 

Since its discovery in 1974, more than 180 papers have been published on the use of the Overmann rearrangement to prepare allylic amines and their analogs from their allylic alcohols. For example, a recent synthesis of the fluoroalkene peptidomimetic precursor of A -acetyl-Z,-glutamyI-Z.-alanine involves the Overman rearrangement of the imidate derived from the allylic alcohol 60. ° This alcohol is readily prepared through Evans asymmetric aldol reaction of oxozolidinone with an aldehyde. 

The synthesis of a fully functionalized cyclopentane core structure of pactamycin, a potent antitumor antibiotic, involves Overman rearrangement as a key reaction. Heating a mixture of potassium carbonate and the imidate derived from allylic alcohol 68 in p-xylene yields the desired trichloroacetamide 69 as a single isomer in 90% yield from 68. In this reaction, potassium carbonate is a crucial additive as no desired product is obtained when the same reaction is carried out without potassium carbonate. Trichloroacetimidate 69 has been elaborated into the tricyclic compound 70 which contains all the carbon atoms for the core cyclopentane of pactamycin, 

The Overman rearrangement of the disubstituted allylic trichloroace-timidates has also been used in the construction of trisubstituted carbons bearing a nitrogen substituent. For instance, heating a solution of the imidate 71 in refluxing xylene fiimishes the allylic trichloroacetamide 72 in good yield. Compound 72 is a precursor to aminocyclopentanol Ti  

Similarly to the mechanism of the Claisen rearrangement, the Overman rearrangement is a suprafacial, concerted, nonsynchronous / 3,37-sigmatropic rearrangement. The reaction is irreversible, which is the result of the significant driving force associated with the formation of the amide functionality. The mechanism of the metal catalyzed reaction is believed to proceed via an iminomercuration-deoxymercuration sequence and it is only formally a [3,3]-sigmatropic shift. 

The Overman rearrangement was used by S.J. Danishefsky et al. to introduce the nitrogen atom stereoselectively at the C4a position of (+)-pancratistatin. The cyclic allylic alcohol was converted to the trichloroacetimidate in the presence of sodium hydride. The compound was heated as a neat liquid under high vacuum, which afforded the desired rearranged product in reasonable yield. 

The transition metai cataiyzed Overman rearrangement allows the reaction to take place at or around room temperature, so thermally sensitive substrates can be used. In the laboratory of M. Mehmandoust, this approach was applied for the synthesis of enantiomerically pure ( )- 3,y-unsaturated a-amino acids, which are potent enzyme inhibitors. ° The trichloroimidate substrates were derived from optically pure monoprotected diallylalcohols and were exposed to 10 mol% of Pd -salt. The rearrangements took place rapidly at room temperature with complete transfer of chirality. 

The asymmetric total synthesis of the phenanthroquinolizidine alkaloid (-)-cryptopleurine was reported by S. Kim et al. One of the key steps in the sequence was the thermai Overman rearrangement which took place in refluxing toluene in nearly quantitative yield and without any loss of the optical purity of the allyl trichloroimidate substrate. 

SCHEME 9.7 Synthesis of sugar aUytic amines employing the Overman rearrangement. 

SCHEME 9.8 Ebata s rare example of the ring contraction as a result of the Baeyer-ViUiger rearrangement. 

Stereoselective transformation of allylic alcohol to allylic trichloroacetamide via trichloroacetimidate intermediate. 

Eukuda, Y. Nishikawa, T. Chabert, P. Kawai, T. Goto, T. Tetrahedron Lett. 1990, 31, 3327. 

Martin, C. Prunck, W. Bortolussi, M. Bloch, R. Tetrahedron Asymmetry 2000, 11, 1585. 

Stereoselective transformatioii of allylic alcohol to allyhc trichloroacetamide via trichloroacetimidate intemiediate. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 186, Springer-Verlag Berlin Heidelberg 2009 

Hifmann, J. Parrot-Lopez, H. Goekjian, P. Tetrahedron Lett. 2007, 48, 6177-6180. 

Overman rearrangement. In Name Reactions for Homologations-Part II Li, J. J., Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2009, pp 210-225. (Review). 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 199, Springer International Publishing Switzerland 2014 

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The synthesis started with levoglucosenone 4, available by the pyrolysis of cellulose, e.g. old newspapers. Bromination-dehydrobromination gave the enantiomerically-pure Diels-Alder dienophile 5, which was combined with isoprene to give predominantly the crystalline adduct 1. Hydrolysis and acetylation led to 6, which was carried on to the geometrically-defined allylic alcohol 7 via reduction with Zn-Cu couple. Overman rearrangement of 7 proceeded with high facial control, to give 8. 

The Overman Rearrangement allows the conversion of readily available allylic alcohols into allylic amines by a two-step synthesis involving the rearrangement of an allylic trichloroacetimidate to an allylic trichloroacetamide with clean 1,3-transposition of the alkenyl moiety. 

Very recently Sutherland and coworkers merged the Pd-catalyzed Overman rearrangement with RCM and ATRC (Fig. 44) [256]. Treatment of dienols 179 with trichloroacetonitrile in the presence of 10 mol% Pd(MeCN)2Cl2 afforded the non-isolated trichloroacetimidate 180, which underwent the [3,3] rearrangement to /V-dienyltrichloroacetamides 174. They were immediately subjected to the RCM/ ATRC sequence using 10 mol% of 145. When chiral cobalt complex (S)- or (R)-181 was used as the catalyst for the Overman rearrangement, indolinones 177 were isolated in 51-70% yields and 89-94% ee. 

Fig. 44 Ruthenium-catalyzed tandem Overman rearrangement/RCM/ATRC reactions...

The Overman rearrangement, a thermal [3,3]-sigmatropic rearrangement of allylic trichloroacetimidates, is an attractive procedure for the preparation of ally] amines from allyl alcohols (Eq. (4)) [7]. 

Several applications of the Overman rearrangement for different type of substrates have been published and some examples can be found in [13],... 

Stereoselective rearrangement reactions can involve sugar-linked functionalities. An example of this type is the Overman rearrangement of allylic trichloracetimidates formed from a D-glucofuranose derivative 20 [36]. This methods affords (L)-a-ami-no acids 25 from (Z)-allylic imidate 23 and (R)-a-amino acids 25 from ( )-imidates 23 with a diastereoselectivity of about 16 1. The oxidative cleavage of compound 24 with Ru04 yields the a-amino acid 25, (Scheme 15). 

SCHEME 10.79 The stereochemical course of the Overman rearrangement of trichloroacetimidates can be influenced using sugar-derived auxiliaries. 

Eguchi, T, Koudate, T, Kakinuma, K, The Overman-rearrangement on a diacetone-D-glucose template, Tetrahedron, 49, 4527-4540, 1993. 

Another example of the use of Wittig products is shown in Scheme 11.35. Two total syntheses by Chida s group made use of the Overman rearrangement to introduce nitrogen functionality on a tertiary carbon atom [109,110]. This was illustrated by the construction of lactacystin 143, a potent neurotrophic factor found in Streptomyces culture broth. 

The rearrangement of allyl trichloroacetimidate into allyl trichloroacetamide (Overman rearrangement) has been used for the synthesis of amino sugars. For example, the trichloroace-... 

In the recent total synthesis of sphingofungin E (90), Overman rearrangement of an allylic trichloroacetimidate derived from diacetone-D-glucose 91 generated tetra-substituted carbon... 

Overhand, Overkleeft and their collaborators have synthesised a variety of SAAs [39]. The synthesis of Fmoc-protected 6 ( Fig. 2) is illustrated in Scheme 2 [15]. Tri-O-acetyl-D-glu-cal was converted into the SAA precursor 43 in five steps. Formation of the trichloroacetimi-date derivative 44 and a subsequent Overman rearrangement was used to introduce the amino group onto the pyran scaffold giving 45. Hydrogenation of the olefin in 45 was accompanied by cleavage of the silyl ether to afford the primary alcohol which was oxidised with a catalytic amount of ruthenium (III) chloride in the presence of sodium periodate giving 46. Subjection... 

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